| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
hDHODH-IN-1 targets human dihydroorotate dehydrogenase (hDHODH), a class 2 mitochondrial enzyme that catalyzes the fourth and rate-limiting step of de novo pyrimidine biosynthesis, converting dihydroorotate to orotate. DHODH is essential for the proliferation of rapidly dividing cells, including activated lymphocytes, cancer cells, and cells of the immune system. By inhibiting DHODH, the compound depletes intracellular pyrimidine pools, which limits DNA and RNA synthesis and suppresses cell proliferation. hDHODH-IN-1 exhibits anti-inflammatory effects, likely through the suppression of lymphocyte proliferation and the production of inflammatory cytokines. The compound serves as a valuable tool for studying DHODH biology and developing therapies for diseases involving dysregulated pyrimidine metabolism.
|
|---|---|
| ln Vitro |
hDHODH is a class 2 dihydroorotate dehydrogenase. Because DHODH is essential for the viability of proliferating cells, inhibitors have been designed to limit human DHODH (hDHODH) activity, which has been linked to cancer, multiple sclerosis, autoimmune and inflammatory disorders [1].
In vitro, hDHODH-IN-1 is a selective inhibitor of human dihydroorotate dehydrogenase (hDHODH). The compound exhibits anti-inflammatory effects. By inhibiting DHODH, the compound depletes intracellular pyrimidine pools, which limits DNA and RNA synthesis and suppresses the proliferation of rapidly dividing cells. This mechanism underlies its anti-inflammatory activity, as the proliferation of activated lymphocytes is dependent on de novo pyrimidine biosynthesis. hDHODH-IN-1 provides a valuable research tool for exploring metabolic vulnerabilities of rapidly dividing cells and for investigating pyrimidine biosynthesis-dependent signaling pathways. The compound's activity is concentration-dependent, with efficacy observed at various concentrations depending on the assay and cell type. |
| ln Vivo |
In vivo, hDHODH-IN-1 has potential applications in inflammatory diseases, autoimmune diseases, and multiple sclerosis. As an hDHODH inhibitor with anti-inflammatory effects, the compound would be expected to suppress lymphocyte proliferation and reduce inflammation in animal models. DHODH inhibitors such as leflunomide and teriflunomide are clinically used for the treatment of rheumatoid arthritis and multiple sclerosis, respectively. hDHODH-IN-1 may offer improved selectivity or potency compared to these agents. However, detailed in vivo efficacy, pharmacokinetic, and toxicological data for hDHODH-IN-1 require further investigation from primary research publications.
|
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for hDHODH-IN-1 involve measuring inhibition of human recombinant DHODH enzymatic activity. The assay typically uses a colorimetric method detecting the conversion of dihydroorotate to orotate coupled with the reduction of the electron acceptor (e.g., 2,6-dichloroindophenol, DCIP). The enzyme is incubated with varying concentrations of the compound, substrate (dihydroorotate), and coenzyme (ubiquinone or decylubiquinone) in assay buffer (typically 50 mM Tris-HCl, pH 8.0, with 0.1% Triton X-100). The reaction is monitored spectrophotometrically by following the decrease in absorbance at 600 nm (DCIP reduction). IC₅₀ values are calculated from concentration-response curves.
|
| Cell Assay |
In vitro cellular experiments with hDHODH-IN-1 are performed using various cell lines to assess its effects on cell proliferation and inflammation. Lymphocytes, cancer cells, or other proliferating cell lines are cultured in appropriate media and treated with varying concentrations of the compound for 24-72 hours. Cell proliferation is assessed using [³H]thymidine incorporation, MTT, or CellTiter-Glo assays. Anti-inflammatory effects may be assessed by measuring the production of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β) using ELISA or by measuring the expression of inflammatory markers using RT-qPCR. The compound's effects on pyrimidine nucleotide levels may be measured using LC-MS. Cells are maintained at 37°C in 5% CO₂ with appropriate media supplements.
|
| Animal Protocol |
In vivo animal studies with hDHODH-IN-1 have not been extensively reported. For inflammatory disease models, standard in vivo studies include collagen-induced arthritis (CIA) for rheumatoid arthritis, experimental autoimmune encephalomyelitis (EAE) for multiple sclerosis, or other models of autoimmune and inflammatory diseases. Mice or rats are treated with hDHODH-IN-1 via oral, intraperitoneal, or intravenous administration at various doses and schedules. Efficacy is assessed by measuring clinical scores, inflammatory markers, histopathological examination of affected tissues, and immune cell infiltration. Pharmacodynamic markers such as DHODH inhibition and pyrimidine nucleotide levels may be measured to confirm target engagement.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of hDHODH-IN-1 are not extensively characterized. The compound has molecular formula C₁₇H₁₄N₂O₂ and molecular weight 278.31. As a small molecule (molecular weight 278.31), it is expected to have reasonable oral bioavailability and tissue distribution. The compound's anti-inflammatory effects suggest it reaches therapeutic concentrations in target tissues. Storage: powder at -20°C for 3 years or 4°C for 2 years. Detailed pharmacokinetic parameters including half-life, clearance, and bioavailability require further investigation from primary research publications.
|
| Toxicity/Toxicokinetics |
Toxicological information for hDHODH-IN-1 is not extensively detailed in the available literature. As a research compound with enzyme inhibitory activity, it should be handled with appropriate safety precautions. Standard safety guidelines for handling potent pharmaceutical compounds apply, including use of personal protective equipment (gloves, safety goggles, lab coat), working in a well-ventilated area, and proper chemical waste disposal. The compound is intended for research use only and is not approved for human therapeutic use. Cytotoxicity studies in cell-based assays help establish the therapeutic window and selectivity index of the compound.
|
| References | |
| Additional Infomation |
hDHODH-IN-1 (CAS 1173715-42-8) is a selective inhibitor of human dihydroorotate dehydrogenase (hDHODH), a class 2 mitochondrial enzyme essential for de novo pyrimidine biosynthesis. The compound has molecular formula C₁₇H₁₄N₂O₂ and molecular weight 278.31. hDHODH-IN-1 exhibits anti-inflammatory effects. The compound provides a valuable research tool for exploring metabolic vulnerabilities of rapidly dividing cells and for investigating pyrimidine biosynthesis-dependent signaling pathways. DHODH is essential for the survival of proliferating cells, and its inhibition has been linked to cancer, inflammatory diseases, autoimmune diseases, and multiple sclerosis. Purity is typically ≥98%. Storage: powder at -20°C for 3 years or 4°C for 2 years.
|
| Molecular Formula |
C17H14N2O2
|
|---|---|
| Molecular Weight |
278.305263996124
|
| Exact Mass |
278.105
|
| CAS # |
1173715-42-8
|
| PubChem CID |
54727972
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
21
|
| Complexity |
447
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(/C(/C#N)=C(/C)\O)NC1C=CC(=CC=1)C1C=CC=CC=1
|
| InChi Key |
MUVPBAIVOHJDOC-VBKFSLOCSA-N
|
| InChi Code |
InChI=1S/C17H14N2O2/c1-12(20)16(11-18)17(21)19-15-9-7-14(8-10-15)13-5-3-2-4-6-13/h2-10,20H,1H3,(H,19,21)/b16-12-
|
| Chemical Name |
(Z)-2-cyano-3-hydroxy-N-(4-phenylphenyl)but-2-enamide
|
| Synonyms |
hDHODHIN1; hDHODH IN 1
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~898.28 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5931 mL | 17.9656 mL | 35.9312 mL | |
| 5 mM | 0.7186 mL | 3.5931 mL | 7.1862 mL | |
| 10 mM | 0.3593 mL | 1.7966 mL | 3.5931 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
